Orphanet Journal of Rare Diseases 2015, Volume 10 Suppl 1 http://www.ojrd.com/content/10/S1/I1 MEETING ABSTRACTS Open Access First European Congress on Hereditary ATTR amyloidosis Paris, France. 2-3 November 2015 Published: 2 November 2015 These abstracts are available online at http://www.ojrd.com/supplements/10/S1 INVITED SPEAKER PRESENTATIONS Rice ASC, Rowbotham M, Sena E, Siddall P, Smith B, Wallace M: Pharmacotherapy for neuropathic pain in adults: systematic review, meta- Lancet Neurol I1 analysis and NeuPSIG recommendations. 2015, 14:162-73. Symptomatic therapy in ATTR amyloidosis: pain killers in TTR-FAP Nadine Attal I2 INSERM U-987, Centre dÂ’’Evaluation et de Traitement de la Douleur, CHU Neuropathic phenotypes and natural history of FAP Ambroise Parc APHP, F-92100 Boulogne-Billancourt, France and University David Adams Versailles Saint-Quentin, Versailles, F-78035, France Centre Paris-Sud, APHP, Hopital de Bicetre and Centre de Reference National E-mail: [email protected] des Neuropathies Amyloides Familiales, 94275 Le Kremlin-Bicetre, France Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):I1 Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):I2 Familial amyloidosis typically causes a nerve length-dependent small fiber TTR-FAP have been described more than 60 years ago by Corino Andrade polyneuropathy that starts in the feet with loss of temperature and pain in Porto (Brain, 1952). This peculiar disease affected many families with an sensations, associated with autonomic dysfunction, which can be extremely autosomal dominant transmission, in the third decade of life, characterized severe and life threatening. Neuropathic pain is commonly associated with by a progressive peripheral neuropathy starting in the lower extremities amyloid neuropathy. There are no randomized controlled trials in peripheral with initial impairment of thermal and pain sensibilities associated with neuropathies specifically related to familial amyloidosis. However meta- gastrointestinal disorders and loss of weight. Natural history has been analyses have confirmed that the efficacy of drugs against neuropathic pain reported by Paula Coutinho (1980) with progression in 3 stages of the generally is not linked to the aetiology of pain and therefore the drugs found disease : stage 1, a disease limited to the lower limbs and a patient is still effective in other painful polyneuropathies may benefit to patients with walking without any help (5.6 years), stage II progressive motor loss in the amyloid neuropathies [1]. Recently the Neuropathic Pain Special Interest lower limbs with steppage needing help for walking (4.8 years), and a Group (NeuPSIG) of the International Association for the Study of Pain has stage III in which the patient is bedridden or confined to a wheelchair updated evidence-based recommendations for pharmacotherapy of (2.3 years). Death comes within an average time of 10.8 years. Late onset neuropathic pain [1] using the Grading of Recommendations Assessment, (LO>50 years) cases of V30M were reported in the 2000’s, with a different Development, and Evaluation (GRADE) system. Pregabalin, gabapentin, phenotype marked by all sensory modalities involvement, relatively mild serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants autonomic symptoms, predominantly in male patients and sporadic cases particularly duloxetine, and tricyclic antidepressants (TCAs) received strong (50%). Three new phenotypes have been described in late onset cases GRADE recommendations for use and are recommended as first-line for more recently: upper limb onset neuropathy, ataxic neuropathy and motor peripheral neuropathic pain, although with caution as regards TCAs. Capsaicin neuropathy. In LO V30M, there is an earliest and rapid impact on high concentration patches, lidocaine patches and tramadol received weak locomotion, need for aid for walking within 3 years from onset, and a GRADE recommendation for use and are recommended as generally second shorter survival 7.3 years (Koike et al, JNNP 2012). There is genotype line for peripheral neuropathic pain and local pain generator. Strong opioids impact on severity and progression of the neuropathy and a correlation of and botulinum toxin type A (BTX-A received weak GRADE recommendations Neuropathy Impairment Scores (NIS) and locomotion score PND (Adams for use mainly because of efficacy in most trials but safety concerns (opioids) et al, Neurology 2015 ; Mariani et al, in press). The phenotype variety, or lower quality of evidence (BTX-A). These drugs are recommended as third frequent absence of family history and autonomic dysfunction in late line by specialist use as regards BTX-A. There was a weak GRADE onset cases contribute to delay diagnosis. The early and increase uptake of recommendation against the use of oromucosal cannabinoids (Sativex) and TTR gene testing should allow to increase the identification of TTR-FAP. valproate and strong GRADE recommendations against the use of levetiracetam and mexiletine because of generally negative results and safety concerns (mexiletine). Other drug treatments (e.g. other antiepileptics, I3 antidepressants and topical treatments, tapentadol and NMDA antagonists) or Which assessment for the carriers: the cardiac view combination therapy received inconclusive GRADE recommendations because Arnt V Kristen of generally discrepant findings, although some of these drugs might be Amylodosis Center, Department of Cardiology, University of Heidelberg, effectiveinsubgroupsofpatients.Thesedrugscanberecommendedin Germany familial amyloid neuropathy, but topical agents have a major advantage in Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):I3 this context because of their low risk of systemic side effects. Reference Cardiac manifestation is common in transthyretin-related (ATTR) 1. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, amyloidosis. However, the age of onset of first symptoms ranges widely. Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SR, Moreover, it differs between the individual mutations. © 2015 Attal This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated. Orphanet Journal of Rare Diseases 2015, Volume 10 Suppl 1 Page 2 of 41 http://www.ojrd.com/content/10/S1/I1 Potential treatment options to disrupt amyloid fibrils are lacking and order to select relevant articles. Additionally, clinical experience achieved cardiac manifestation is associated with poor prognosis. Thus, early by lead investigators and our own experience was applied in this analysis. identification of patients at risk for development of systemic ATTR Results: Nowadays siRNA (Patisaran®), Antisense Oligonucleotides, amyloidosis is crucial to avoid deterioration of organ function and Diflunisal and Doxycicline-TUDCA are under clinical trial investigation. maintain quality of life. Predictive moleculargenetic testing of family Election criteria definition is essential to enroll a patient in one of those members is the initial step to identify a patient at risk for hereditary ATTR clinical trials. Based on the bibliography, inclusion criteria protocols of amyloidosis. However, incomplete penetrance and high variability of age each clinical trial and our own experience the following criteria have of onset of disease complicates the diagnostic strategy. Thus, regular been developed: screening is required for early identification of the disease. However, the question arises what diagnostic tools should be used for assessment of 1. Stage I to Stage IIIB can be recruited into a clinical trial at any asymptomatic carriers of a TTR gene variant. time. Although endomyocardial biopsy has the highest sensitivity and specificity 2. Stage I non-respondents to Tafamidis after 12 months treatment for detection of cardiac amyloidosis it is not capable for longitudinal who show progression of the disease indicated by. evaluation in asymptomatic carriers. Non-invasive strategies are required • Worsening of ambulation (increase of PND score by one point). to allow frequent testings with time intervals ranging between 6 and • Onset of orthostatic hypotension or impotence. 24 months. ECG, echocardiography, cardiac magnetic resonance imaging, • Progress of cardiomyopathy with worsening of stage of cardiac skeletal scintigraphy, and cardiac biomarkers are potential tools for insufficiency NYHA by 1 point or of cardiac conduction assessment. In general, routine assessment should be based on ECG and disorders. echocardiography. Precise screening of ECG for any abnormalities 3. It is expected than in the short future OLT patients who including conduction disturbances, QRS or T-wave abnormalities is mandatory as abnormal findings are present in almost all patients with underwent illness progression would be enrolled in a clinical trial. cardiac ATTR amyloidosis. Echocardiography assessment should include Conclusions: Disease staging, tafamidis response and OLT limitations are evaluation of diastolic function, longitudinal impairment, as well as speckle the main factors to be considered before recruiting a patient for a clinical tracking. Cardiac